The leukotrienes are extremely potent substances which produce a wide variety of biological effects, often in the nanomolar to picomolar concentration range. Leukotrienes are important pathological mediators in a variety of diseases. Alterations in leukotriene metabolism have been demonstrated in a number of disease states including asthma, allergic rhinitis, rheumatoid arthritis and gout, psoriasis, adult respiratory distress syndrome, inflammatory bowel disease, endotoxin shock syndrome, atherosclerosis, ischemia induced myocardial injury, and central nervous system pathology resulting from the formation of leukotrienes following stroke or subarachnoid hemorrhage.
Compounds which prevent leukotriene biosynthesis are thus useful in the treatment of disease states such as those listed above in which the leukotrienes play an important role.
U.S. Pat. No. 4,970,215 to Mohrs, et al. discloses and claims certain 4-(quinolin-2-yl-methoxy)phenyl-cycloalkyl acetic acids for inhibition of leukotriene synthesis.
European Patent Application 0 349 062 to Zamboni, et al. discloses and claims certain quinolylmethoxyphenyl substituted thioalkanoic acid derivatives as leukotriene biosynthesis inhibitors.
The publication of Prosit, et al. in Bioorganic and Medicinal Chemistry Letters, 1991,1:645-648 describes a new, potent and orally active leukotriene synthesis inhibitor, L-674,636 ({[4-(4-chlorophenyl)-1-(4-[2-quinolinylmethoxylphenyl)butyl]thio}acetic acid).